title: Three novel mutations in the carnitine-acylcarnitine translocase (CACT) gene in patients with CACT deficiency and in healthy individuals.
abstract: Carnitine-acylcarnitine translocase (CACT) and carnitine palmitoyltransferase II (CPT2) are key enzymes for transporting long-chain fatty acids into mitochondria. Deficiencies of these enzymes, which are clinically characterized by life-threatening non-ketotic hypoglycemia and rhabdomyolysis, cannot be distinguished by acylcarnitine analysis performed using tandem mass spectrometry. We had previously reported the CPT2 genetic structure and its role in CPT2 deficiency. Here, we analyzed the CACT gene in 2 patients diagnosed clinically with CACT deficiency, 18 patients with non-traumatic rhabdomyolysis and 58 healthy individuals, all of whom were confirmed to have normal CPT2 genotypes. To facilitate CACT genotyping, we used heat-denaturing high-performance liquid chromatography (DHPLC), which helped identify five distinct patterns. The abnormal heteroduplex fragments were subjected to CACT-specific DNA sequencing. We found that one patient with CACT deficiency, Case 1, carried c.576G>A and c.199-10t>g mutations, whereas Case 2 was heterozygous for c.106-2a>t and c.576G>A. We also found that one patient with non-traumatic rhabdomyolysis and one healthy individual were heterozygous for c.804delG and the synonymous mutation c.516T>C, respectively. In summary, c.576G>A, c.106-2a>t and c.516T>C are novel CACT gene mutations. Among the five mutations identified, three were responsible for CACT deficiency. We have also demonstrated the successful screening of CACT mutations by DHPLC.
authors.affiliation: Division of Nephrology and Rheumatology, Department of Internal Medicine, Fukuoka University School of Medicine, Fukuoka, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Fukushima
authors.affiliation: 1] Division of Nephrology and Rheumatology, Department of Internal Medicine, Fukuoka University School of Medicine, Fukuoka, Japan [2] Division of Medical Sciences, Fukuoka University School of Nursing, Fukuoka, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Kaneoka
authors.affiliation: Division of Nephrology and Rheumatology, Department of Internal Medicine, Fukuoka University School of Medicine, Fukuoka, Japan.
authors.forename: Tetsuhiko
authors.initials: T
authors.lastname: Yasuno
authors.affiliation: Division of Medical Sciences, Fukuoka University School of Nursing, Fukuoka, Japan.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Sasaguri
authors.affiliation: Division of Medical Sciences, Fukuoka University School of Nursing, Fukuoka, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Tokuyasu
authors.affiliation: Department of Neonatal Medicine, Gifu Prefectural General Hospital, Gifu, Japan.
authors.forename: Kuniko
authors.initials: K
authors.lastname: Tokoro
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Fukao
authors.affiliation: 1] Division of Nephrology and Rheumatology, Department of Internal Medicine, Fukuoka University School of Medicine, Fukuoka, Japan [2] General Medical Research Center, Fukuoka University School of Medicine, Fukuoka, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Saito
mesh_terms: D000328:Adult; D002333:Carnitine Acyltransferases / Q000172:deficiency* / Q000235:genetics; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics; D016022:Case-Control Studies; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D006801:Humans; D008052:Lipid Metabolism, Inborn Errors / Q000235:genetics*; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*
chemical_list: D026901:Membrane Transport Proteins; C120109:SLC25A20 protein, human; D002333:Carnitine Acyltransferases; D002334:Carnitine O-Palmitoyltransferase